The chondrocyte is a phenotypically heterogenous cell type suggesting that multiple molecular determinants control its differentiation. We are interested in identifying transcription regulators of chondrocyte differentiation. In particular we are interested in the role of Cbfa proteins, that are known to act as cell differentiation factors in several lineages, during this process. We have shown previously that Cbfa1 is expressed early during development in a common progenitor for chondrogenic zones, however, its role during chondrocyte differentiation could not be analyzed because of the early lethality of Cbfa-deficient embryos. We propose here to perform a systematic analysis of Cbfa2 expression pattern during chondrogenesis and to use genetic means to decipher its role in this process by deleting or over-expressing this gene only in chondrocytes. The specific aims are: To perform a complete and comparative study of the pattern of expression of Cbfa and Cbfa1 by in situ hybridization and immunocytochemistry. To generate and study the phenotype of chondrocyte-specific Cbfa2- deficient mice. To generate transgenic mice expressing permanently Cbfa1 in chondrocytic cells and to analyze their phenotype. To study any cross regulation between Cbfa2 and Cbfa1.